[Chondroma and chondrosarcoma of the respiratory system].
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Chondroma↗
Biomedical subjects
T Murate
Publications and source records attributed to T Murate.
The close relationship between DNA replication and the selection of differentiation lineages of human erythroleukemia cell lines K562, HEL, and TF1 into either erythroid or megakaryocytic lineages.
The selection of differentiation lineages into either erythroid or megakaryocytic series was analyzed with human erythroleukemia cell lines K562, HEL, and cytokine-dependent TF1. A tumor promoter, TPA, induced a megakaryocyte marker, glycoprotein IIb/IIIa (GP IIb/IIIa) or IIIa (GP IIIa), but suppressed erythroid differentiation. On the other hand, aphidicolin, which is a potent inhibitor of DNA replication, inhibited GP IIb/IIIa or IIIa expression, but induced the expression of erythroid phenotypes. These phenomena were observed in all erythroleukemia cell lines tested. The bromodeoxyuridine labeling experiments indicated that de novo DNA synthesis was completely suppressed by aphidicolin treatment but was well preserved in TPA-treated cells. Among these three cell lines, erythropoietin (EPO) treatment induced erythroid differentiation of TF1 cells, which was dependent on GM-CSF or IL-3. In this case, EPO functioned as the survival factor and mild stimulator for cell proliferation as well as the inducer of erythroid differentiation. However, when either GM-CSF or IL-3 was depleted from the culture medium, TF1 ceased cell growth; concomitantly, hemoglobin-positive cells appeared, which is consistent with the results obtained with aphidicolin. The incubation of K562 cells for 48 h with either TPA or aphidicolin induced the irreversible commitment of cells to megakaryocytic and erythroid lineages, respectively. Our results using three different erythroleukemia cell lines suggest that a possible linkage between the DNA replication system and the selection of a differentiation lineage is the common feature of human erythroleukemia cell lines, and that these culture systems provide a suitable model for the analysis of the signal transduction system for differentiation lineage selection.
Aphidicolin↗
Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small-cell lung cancer.
Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.
Adult↗
Induction of neutrophil alkaline phosphatase gene expression by granulocyte colony-stimulating factor in chronic myelogenous leukemia.
The mechanism underlying defective neutrophil alkaline phosphatase (NAP) activity in chronic myelogenous leukemia (CML) was examined using Northern blotting analysis and NAP staining. Fourteen patients with Ph1-positive CML in the chronic phase were included in this study. Polymorphonuclear cells (PMN), containing more than 80% of stab and segmented neutrophils, were collected from peripheral blood (PB) by methylcellulose sedimentation after density gradient centrifugation. Neutrophil alkaline phosphatase mRNA (NAPmRNA) expression was very weak in all patients. When incubated with granulocyte colony-stimulating factor (G-CSF) for 24 h, the PMN of all patients expressed a detectable level of NAPmRNA. NAP score, which semiquantitatively reflects the activity of gene products, was also elevated after incubation with G-CSF in 12 patients. However, a higher dose of G-CSF was required for the maximum response than was the case for normal bone marrow PMN, which also manifested increases of NAPmRNA and its products on stimulation by G-CSF. The present study suggests that the PMN of CML express NAPmRNA and produce its products in response to G-CSF, but that they are less sensitive to G-CSF than normal bone marrow PMN.
Adolescent↗
Erythroid potentiating activity of tissue inhibitor of metalloproteinases on the differentiation of erythropoietin-responsive mouse erythroleukemia cell line, ELM-I-1-3, is closely related to its cell growth potentiating activity.
The erythroid-potentiating activity (EPA) of the tissue inhibitor of metalloproteinase-1 (TIMP-1) was re-examined using ELM-I-1-3, a mouse erythroleukemia cell line, which responded well to erythropoietin. Depletion of pre-existing TIMP-1 from fetal calf serum in culture medium using monoclonal antibody suppressed erythropoietin-induced differentiation as measured by the induction of hemoglobin, commitment assay and globin mRNAs. The removal of TIMP-1 also suppressed the proliferation of ELM-I-1-3 as measured by cell number and de novo DNA synthesis. These changes were reversed by the addition of purified TIMP-1 to the culture medium. Anti-TIMP-1 antibody also blocked both hexamethylene bisacetamide (HMBA)-induced erythroid differentiation and the proliferation of both ELM-I-1-3 and Friend erythroleukemia cells. Considering previous reports analyzing the chemical induction of Friend mouse erythroleukemia cell differentiation, our results suggest that erythropoietin- or HMBA-induced erythroid differentiation might also be coupled with cell proliferation. Our 3H thymidine-uptake experiment shows that TIMP-1 removal was also effective in the inhibition of cell growth of various other cell lines in addition to erythroleukemia cell lines. These results suggest that EPA action of TIMP-1 on erythroid leukemia cell lines is closely related to its activity to promote the cell growth of various cell lines and cells including erythroleukemia cell lines.
Acetamides↗
Thrombin-induced shape change in human megakaryoblastic leukemic cells, MEG-01, is mediated by protein kinase C.
We investigated the intracellular processes of the shape change in human megakaryoblastic leukemic cells, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by phorbol 12-myristate 13 acetate (TPA) and weakly by Ca2+ ionophore, A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC-labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells by thrombin. Shape change was inhibited by cytochalasin B. Since Ca(2+)-dependent phosphorylation reactions play central role on the initiation of shape change of platelet, we examined the effects of protein kinase C (PKC) inhibitor, H-7, and myosin light chain (MLC) kinase inhibitor, ML-9, on the shape change of MEG-01 cells induced by thrombin, and observed that H-7 potently inhibited thrombin-induced shape change, while ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC, but not by MLC kinase.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
[A case of pure red cell aplasia with monoclonal gammopathy].
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Bone Marrow Cells↗
Chest roentgenogram classification and clinical parameters in patients with active pulmonary tuberculosis.
The relationship between the clinical parameters and chest film appearance was studied in patients with active pulmonary tuberculosis. Patients with extended disease were often malnourished and had weak tuberculin reaction accompanied by lymphopenia. They excreted a large amount of mycobacterial bacilli and a longer period was required for negative conversion of sputum culture. We confirmed that the criteria for chest roentgenogram classification established by the Japanese Society for Tuberculosis ("Gakkai Classification") is useful in the estimation of the risk of infection and the prognosis of tuberculosis patients.
Adolescent↗
[A case of carcinosarcoma of the lung].
A 78-year-old man was admitted to our hospital with cough and left anterior chest pain. Chest X-ray examination on admission revealed a tumor shadow in the left upper lobe. Malignant tumor cells were observed on histopathological examination of a specimen obtained by bronchoscopic biopsy. Radiotherapy was performed but was not effective, and the patient died of respiratory failure 4 months after admission. Autopsy revealed a 15 cm diameter tumor with marked local invasion tendency without distant metastasis. Microscopically, the tumor consisted partly of squamous cell carcinomas, and partly of fibrosarcomas, composed of spindle cells and osteo-chondrosarcoma. The tumor was therefore diagnosed as carcinosarcoma. Immunohistochemical examination showed positive keratin and EMA staining only in the squamous cell carcinoma component of the tumor.
Aged↗
Aphidicolin, an inhibitor of DNA replication, blocks the TPA-induced differentiation of a human megakaryoblastic cell line, MEG-O1.
The commitment process of a human megakaryoblastic cell line (MEG-O1) induced with phorbol ester, TPA, was investigated with special reference to glycoprotein (GP) IIb/IIIa expression, multinuclear formation, and DNA replication. TPA (10(-7) mol/L) completely inhibited cellular division in MEG-O1, but did not suppress de novo DNA synthesis. Two days' culture with 10(-7) mol/L TPA was sufficient for MEG-O1 cells to initiate an irreversible commitment process. These cells could not resume cell growth and expressed GP IIb/IIIa antigen; some of them showed multinuclear form and DNA polyploidy even after removal of TPA from the culture medium. DNA histogram analysis showed that, upon treatment with TPA, the percentage of cells whose DNA ploidy was more than 8N was 5 to 10 times higher than that of control cells. Precise analysis using cell size fractionation by centrifugal elutriation method showed that there was strong correlation between the percentage of multinuclear cells and DNA polyploidy in TPA-treated cells. The percentage and staining intensity of GP IIb/IIIa and other megakaryocytic phenotypes such as von Willebrand factor and PAS staining were highest in large multinuclear cell populations, suggesting that these cells are the most differentiated population in this system. In TPA-treated cells, the activity of DNA polymerase alpha, a marker for cell growth, remained at the same level as in control cells. Aphidicolin, a specific inhibitor of DNA polymerase alpha, completely inhibited the differentiation induction of MEG-O1 cells with TPA measured by either GP IIb/IIIa expression or multinuclear cell formation. Therefore, DNA replication appears to be involved in the process of phenotypic expression as well as endomitosis in megakaryocyte differentiation of MEG-O1 cells. Aphidicolin was also effective in inhibiting megakaryocytic differentiation of other leukemia cell lines such as human erythroleukemia (HEL) and K562 cell lines induced with TPA, suggesting the close interplay of DNA replication and phenotypic expression in megakaryopoiesis.
Aphidicolin↗
Cytokine content in pleural effusion. Comparison between tuberculous and carcinomatous pleurisy.
Tuberculous pleurisy is a good model for resolution of local cellular immunity. It would be expected that tuberculous pleural fluid contains a variety of immunologically important cytokines because of the accumulation of immunocompetent cells in the pleural cavity. We studied interleukin 1 (IL-1), interleukin 2 (IL-2), and interferon gamma (IFN-gamma) levels in pleural fluid of 20 patients with tuberculous pleurisy and compared them with those in pleural fluid of 20 patients with malignant pleurisy. We also evaluated adenosine deaminase (ADA) levels in both effusions. Tuberculous pleural fluid had higher levels of IL-1, IL-2, IFN-gamma, and ADA than malignant pleural fluid. Although the difference of IL-1 level between tuberculous and malignant pleural fluid was modest, that of IL-2, IFN-gamma, and ADA was dominant. These findings suggest that activated T lymphocytes in tuberculous pleural fluid concern the production of lymphokines at the morbid site and they effectively exert local cellular immunity through the action of such lymphokines.
Adenosine Deaminase↗
[A case of RAEB-t treated by G-CSF showing complete remission after MST-16 treatment for subsequent reversible leukemia].
A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.
Acute Disease↗
[Myelodysplasia predominantly involving in megakaryocytic lineage successfully treated with low-dose Ara-C].
A 17 year old male was admitted because of pancytopenia. Bone marrow aspiration revealed myelodysplasia, no increase of blast cells and excessive expansion of megakaryocytic lineage. Although mild increase of bone marrow reticulin fiber was observed, no hepatosplenomegaly was recognized. Therefore he was diagnosed as refractory anemia (RA) or MDS with myelofibrosis and treated with low dose Ara-C regimen. Remission was achieved in June 1987, but the relapse occurred in Oct. 1987. His bone marrow at the relapse showed more remarkable dysplastic change than before. Sequential bone marrow examinations thereafter, revealed an increase of megakaryocytic lineage, especially immature dysplastic megakaryocytes, leading to the appearance of the abnormal megakaryoblasts (detected with anti GP IIb/IIIa antibody) as well as uncharacterized blast cells in his terminal stage. Transformation from MDS to megakaryocytic leukemia was strongly suggested. He died of severe pneumonia in March 1989. The invasion of abnormal immature megakaryocytic cells including megakaryoblasts was observed in liver, spleen and lymph nodes at autopsy. There are several reports on cases having a common hematological features such as 1) pancytopenia in peripheral blood, 2) myelodysplasia, 3) excessive growth of megakaryocytic lineage, 4) myelofibrosis without hepatosplenomegaly, although other clinical features were different. We propose all these cases should be reviewed at the point of MDS mainly involved in megakaryocytic lineage.
Adolescent↗
Cytogenetic and clonal culture evaluation after response to low dose Ara-C in myelodysplastic syndromes.
Cytogenetic and bone marrow culture studies were performed sequentially in 13 patients with myelodysplastic syndromes (MDS) who responded to low dose cytosine arabinoside (Ara-C) treatment (complete in nine and partial in four patients). Of nine patients with initial clonal karyotypic abnormalities, six recovered a normal karyotype after attaining a response to treatment, but the other three patients retained partial or total karyotypic abnormalities. A new clonal karyotypic abnormality appeared after treatment in one patient. Eight patients showed normal colony growth of both granulocyte-macrophage colony-forming units and erythroid burst-forming units after treatment, but five were still defective. There was a clear difference in the duration of response to treatment between these two groups. Consolidation treatment was not effective in patients with persistent karyotypic abnormalities or defective colony formation. Although the number of patients studied is small, these results suggest that hemopoiesis in patients with MDS following a response to treatment with low dose Ara-C is heterogeneous. Consolidation chemotherapy is recommended to ensure and prolong the response in patients showing normalization of both cytogenetic and bone marrow culture results.
Adolescent↗
Response of leukemic cells to the sequential combination of GM-CSF and G-CSF.
We designed two experiments using delayed stimulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) with colony-type analysis in order to elucidate the characteristics of factor-dependent proliferation and differentiation of leukemic progenitor cells. Eight patients with acute myelogenous leukemia showing non-autonomous colony growth were selected. Three of the six cases showed that delayed addition of G-CSF to agar culture initiated by GM-CSF had no influence on the type and number of colonies; whereas, delayed addition of GM-CSF to G-CSF resulted in additional GM colonies. These findings were the same for normal bone marrow progenitors. In two cases, granulocytic colonies markedly increased with delayed addition of G-CSF to GM-CSF. Synergism occurred in one case where GM-CSF was used first. In the next experiment, regardless of whether CSF was used during the 48 hour preincubation, subsequent colony types were affected by the CSF used in agar culture. But colony numbers increased 1.5 fold in two of six cases by preincubation with GM-CSF, and 1.2 to 1.7 fold in all normal cases by preincubation with G-CSF. These results suggest that although there is a great heterogeneity in the response to CSF, some leukemic progenitors act like normal progenitors.
Colony-Stimulating Factors↗
Terminal differentiation of human erythroleukemia cell line K562 induced by aphidicolin.
To analyze the relationship between differentiation and DNA replication, the effect of aphidicolin, a specific inhibitor for DNA polymerase alpha, was measured with respect to erythroid differentiation and activities of DNA polymerases alpha, beta, and gamma. Five micromolar aphidicolin completely blocked the growth of K562 cells and caused 80% of cells to become hemoglobin positive after 5 days exposure. The cessation of K562 cell growth induced by aphidicolin was irreversible, whereas the inhibition of HeLa cell growth was completely reversible. The enzyme activity of DNA polymerase alpha of K562 cells showed a 50-110% increase with aphidicolin treatment as compared to control K562 cells; activities of DNA polymerases beta and gamma were not affected. These features sharply contrasted with the erythroid induction of the same cells by hemin, where cell growth was not suppressed and DNA polymerase alpha was not increased but rather decreased. The enzyme activity of DNA polymerase alpha remained high even after removal of aphidicolin from the culture medium. These results suggest that treatment with aphidicolin might induce an accumulation of protein factors for replication and/or differentiation, causing rapid cell differentiation of cells without cell division.
Antineoplastic Agents↗
Patchy haemopoiesis in long-term remission of idiopathic aplastic anaemia.
13 patients with idiopathic aplastic anaemia in remission for more than 2 years were examined to define the haemopoietic status by means of bone marrow scintigraphy, ferrokinetics and bone marrow culture for haemopoietic progenitor cells. Haemoglobin levels reached the normal range in all these patients although mild neutropenia and thrombocytopenia were still observed in 5 patients. Bone marrow scintigrams using indium-111 showed normal distribution in 2, diffuse low accumulation in 3, patchy distribution in 7, and expanded distribution with patchy uptake in 1 patient. The defective haemopoiesis was also confirmed by ferrokinetic and bone marrow culture studies. The patchy haemopoiesis appears to characterize the residual marrow damage in remission of idiopathic aplastic anaemia.
Adult↗
Antipurified-protein-derivative antibody in tuberculous pleural effusions.
Using ELISA, we studied anti-PPD antibody values in 31 tuberculous and 39 carcinomatous pleural effusions. Mean ODI values of anti-PPD IgG, IgA and IgM antibodies in tuberculous pleural effusions were higher than those in carcinomatous pleural effusions (p less than 0.01 in IgG and IgA, p less than 0.05 in IgM antibodies). We also analyzed the detected antigens in PPD and BCG whole cell fraction recognized by IgG antibody in tuberculous pleural effusions. Among heteromolecular components, the antigen band from 25 to 40 Kd region was most frequently stained. This antigen was heat-stable, contained sugar components, and included no disulfide bonds.
Adolescent↗